Vitamin D3 analogs are useful for the treatment of hyperproliferative skin diseases, such as psoriasis vulgaris and are involved in essential cell regulatory processes such as proliferation and differentiation in a number of different cell types including cancer cells. The vitamin D3 analog calcitriol has been shown to induce cell growth arrest and to possess differentiation-inducing behavior in both primary melanocytes and melanoma cell lines. It was shown that growth inhibitory effects of calcitriol are mediated by increased levels of p21 in the prostatic carcinoma cell lines. There has also been intense interest in effects of calcitriol on apoptosis, malignant cell invasion and metastasis. It is recognized that calcitriol induces several biological effects influencing a number of signal transduction pathways, and may lead to severe side effects. These biological effects make vitamin D analogs promising candidate agents for cancer therapy. However, the therapeutic efficacy of systemically applied vitamin D analogs for treating cancer has not yet fulfilled its promise. One main reason for these disappointing results is that the use of systemically applied vitamin D analogs is limited by severe side effects, mostly hypercalcemia, at the supraphysiological doses needed to reach clinical improvement.
Calcipotriol is a synthetic derivative of calcitriol and it is used in the treatment of psoriasis. The precise mechanism of calcipotriol in remitting psoriasis is not well-understood. The efficacy of calcipotriol, a vitamin D3 analog, in inhibition of proliferation in a variety of cell types, and its therapeutic potential in the topical treatment of psoriasis has been established in a large number of clinical trials. In vitro studies have shown that calcipotriol stimulates terminal cell differentiation and has antiproliferative effects. In vivo, calcipotriol has been shown to reduce the number of cycling epidermal cells. These properties make calcipotriol an ideal candidate for the topical treatment of hyperproliferative disorders. While it has been approved for topical use in psoriasis, its potential for use in other disorders has not yet been fully investigated.